19-40422858-C-G

Variant names:

• chr19-40422858-C-G
• rs139610928
• NM_013376.4:c.689G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013376.4(SERTAD1):​c.689G>C​(p.Arg230Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,603,288 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R230Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SERTAD1 NM_013376.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

Genes affected

SERTAD1 (HGNC:17932): (SERTA domain containing 1) Predicted to be involved in epigenetic maintenance of chromatin in transcription-competent conformation. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERTAD1	NM_013376.4	c.689G>C	p.Arg230Pro	missense_variant	Exon 2 of 2	ENST00000357949.5	NP_037508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERTAD1	ENST00000357949.5	c.689G>C	p.Arg230Pro	missense_variant	Exon 2 of 2	1	NM_013376.4	ENSP00000350633.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451030 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 720128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74386

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.092
Eigen_PC	Benign	0.066
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.10
Sift	Uncertain	0.013	D
Sift4G	Benign	0.19	T
Polyphen		0.13	B
Vest4		0.65
MutPred		0.37		Gain of glycosylation at R230 (P = 0.0342);
MVP		0.71
MPC		0.52
ClinPred		0.52	D
GERP RS		4.6
Varity_R		0.37
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139610928; hg19: chr19-40928765;